Resistance to cetuximab in HNC

Elkabets (BGU), Baselga and Scaltriti (MSKCC) BSF#2017323 Genotypic and histological characterization of MET pathway in resistance to cetuximab in head and neck cancer Lay-terms abstract Head and neck squamous cell carcinoma (HNSCC) the incidence of is increasing worldwide, has a low survival rate mostly due to late diagnosis, low responsiveness to therapy, and disease recurrence. The most prevalent treatment for HNSCC is a combination of the traditional regimens (chemotherapy, radiation, and surgery) with biological therapies, particularly cetuximab (Erbitux), an antibody that blocks the epithelial growth factor receptor (EGFR). A well-known cell surface protein, EGFR is involved in HNSCC progression and metastasis.

Although cetuximab is effective in HNSCC and is an FDA-approved drug, only a small proportion of HNSCC patients benefit from cetuximab treatment while the rest develop resistance to cetuximab. In fact, the majority of HNSCC patients are therefore treated with an ineffective agent, and currently, biomarkers for predicting responsiveness to cetuximab are lacking.

In the proposed study, we aim to identify the specific pathways involved in the resistance and sensitivity to cetuximab with the ultimate goal of improving the response rate of HNSCC patients treated with this agent. To achieve this goal, we have generated a unique bio-bank of tissue specimens obtained from cetuximab resistant and sensitive tumors from HNSCC patients. By comparing the gene and protein expression levels in these two populations, we will be able to elucidate the intracellular mechanisms underlying responsiveness to cetuximab and possibly to other EGFR-related drugs. Resolving these mechanisms may yield specific markers of response and enable a personalized treatment for this lethal malignancy.

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